De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity

Mengle Shao, Lavanya Vishvanath, Napoleon C. Busbuso, Chelsea Hepler, Bo Shan, Ankit X. Sharma, Shiuhwei Chen, Xinxin Yu, Yu A. An, Yi Zhu, William L Holland, Rana K Gupta

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Pathologic expansion of white adipose tissue (WAT) in obesity is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown. Here, we test the hypothesis that the potential to recruit new adipocytes from Pdgfrβ+ preadipocytes determines visceral WAT health in obesity. We manipulate levels of Pparg, the master regulator of adipogenesis, in Pdgfrβ+ precursors of adult mice. Increasing the adipogenic capacity of Pdgfrβ+ precursors through Pparg overexpression results in healthy visceral WAT expansion in obesity and adiponectin-dependent improvements in glucose homeostasis. Loss of mural cell Pparg triggers pathologic visceral WAT expansion upon high-fat diet feeding. Moreover, the ability of the TZD class of anti-diabetic drugs to promote healthy visceral WAT remodeling is dependent on mural cell Pparg. These data highlight the protective effects of de novo visceral adipocyte differentiation in these settings, and suggest Pdgfrβ+ adipocyte precursors as targets for therapeutic intervention in diabetes.

Original languageEnglish (US)
Article number890
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Shao, M., Vishvanath, L., Busbuso, N. C., Hepler, C., Shan, B., Sharma, A. X., Chen, S., Yu, X., An, Y. A., Zhu, Y., Holland, W. L., & Gupta, R. K. (2018). De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity. Nature Communications, 9(1), [890]. https://doi.org/10.1038/s41467-018-03196-x